VEGF Dimer Column for Preeclampsia Treatment

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Solution Overview

Problem

Current therapeutic approaches for preeclampsia, such as systemic administration of recombinant proteins and extracorporeal apheresis, face challenges including dose-limiting side effects, short half-life of proteins, and non-specific removal of sFlt-1, which disrupts angiogenic balance and poses risks to both mother and fetus.

Innovation Solution

A column comprising a vascular endothelial growth factor (VEGF) dimer molecule is developed, specifically designed to efficiently adsorb sFlt-1 from blood while releasing VEGF and PIGF, thereby restoring angiogenic balance through enhanced affinity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If systemic administration of recombinant VEGF or PIGF is used to treat preeclampsia, then angiogenic balance is improved, but dose-limiting side effects occur in the mother

Engineering Contradiction:

Improveangiogenic balanceVSAvoiddose-limiting side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and removes the harmful sFlt-1 protein from the maternal circulation using an apheresis column, rather than administering more VEGF/PIGF to compensate for sFlt-1 deficiency. This selective removal approach eliminates the source of angiogenic imbalance without exposing the mother to dose-limiting side effects of recombinant protein administration.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention converts the harmful effect of sFlt-1 (which causes endothelial dysfunction) into a beneficial therapeutic target by specifically removing it from circulation. The apheresis column uses immobilized PIGF to selectively bind and remove sFlt-1, transforming the pathogenic molecule into a removable target rather than requiring continuous supplementation.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Quantity of substance

If extracorporeal apheresis is used to remove sFlt-1, then sFlt-1 levels are reduced, but non-specific removal of sFlt-1 disrupts angiogenic balance

Engineering Contradiction:

ImprovesFlt-1 levelsVSAvoidangiogenic balance

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The invention applies local quality by using a specifically designed apheresis column with immobilized PIGF that selectively binds sFlt-1 while preserving other angiogenic factors. The column matrix provides localized binding sites that recognize the specific epitopes on sFlt-1, enabling selective removal without affecting VEGF or PIGF in the circulation.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention uses immobilized PIGF as an intermediary substance on the apheresis column that mediates the selective removal of sFlt-1. The PIGF-VEGF complex formed on the column surface acts as a specific trap for sFlt-1, enabling precise removal while maintaining overall angiogenic balance through the intermediary binding mechanism.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Object-generated harmful factors

If recombinant VEGF is administered to treat preeclampsia, then maternal symptoms are attenuated, but serious dose-limiting side effects occur

Engineering Contradiction:

Improvematernal symptomsVSAvoiddose-limiting side effects

Core Design Contradiction:

Object-generated harmful factorsVSObject-affected harmful factors

Solution Approach 1:

Instead of adding more VEGF to the circulation to treat maternal symptoms, the invention extracts and removes sFlt-1, the molecule causing the symptoms. This extraction approach eliminates the harmful effect without introducing additional recombinant protein that would cause dose-limiting side effects.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention inverts the conventional therapeutic approach by not supplementing VEGF/PIGF levels but rather removing sFlt-1. This inversion transforms the treatment strategy from 'add more growth factor' to 'remove the antagonist', thereby eliminating side effects associated with recombinant protein administration.

Inventive Principle:

Principle #13The other way round (Inversion)

4Reliability

If PIGF is used in apheresis columns to remove sFlt-1, then sFlt-1 binding is achieved, but the short half-life of PIGF limits effectiveness

Engineering Contradiction:

ImprovesFlt-1 bindingVSAvoidPIGF half-life

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The invention applies preliminary action by immobilizing PIGF on the apheresis column matrix before use, creating a stable, long-lasting binding platform. Once PIGF is covalently or firmly attached to the column, it remains in place for repeated use, eliminating the limitation of its short half-life in circulation and providing sustained sFlt-1 removal capability.

Inventive Principle:

Principle #10Preliminary action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The VEGF dimer column achieves significant reduction of sFlt-1 levels and pronounced release of VEGF and PIGF, effectively addressing the imbalance and improving treatment outcomes for preeclampsia with enhanced safety and efficacy.

Implementation Method 1

A column comprising a vascular endothelial growth factor (VEGF) dimer molecule is developed, specifically designed to efficiently adsorb sFlt-1 from blood

Methodology Applied

Scientific EffectAdsorption: Adsorption

Implementation Method 2

releasing VEGF and PIGF, thereby restoring angiogenic balance through enhanced affinity and specificity

Methodology Applied

Scientific EffectRelease from complexes:

Data Source

PatentUS20230119290A1VEGF dimer molecules and columns comprising a VEGF dimer molecule as well as uses, production methods and methods involving the same

Publication Date: 2023.04.20 UNIVERSITY OF COLOGNE

AI summary

The present invention relates to a column comprising a vascular endothelial growth factor (VEGF) dimer molecule, a method for preparing such a column, a VEGF dimer molecule, an expression vector and a recombinant host cell encoding for a VEGF dimer, as well as uses and methods related thereto.